6-87514311-CA-C

Position:

• chr6-87514311-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020320.5(RARS2):​c.*101del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 562,758 control chromosomes in the GnomAD database, including 6,015 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (5428 hom., cov: 0)
  • Exomes 𝑓: 0.32 (587 hom.)
• Consequence: RARS2 NM_020320.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.613

Genes affected

RARS2 (HGNC:21406): (arginyl-tRNA synthetase 2, mitochondrial) This nuclear gene encodes a protein that localizes to the mitochondria, where it catalyzes the transfer of L-arginine to its cognate tRNA, an important step in translation of mitochondrially-encoded proteins. Defects in this gene are a cause of pontocerebellar hypoplasia type 6 (PCH6). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 6-87514311-CA-C is Benign according to our data. Variant chr6-87514311-CA-C is described in ClinVar as [Benign]. Clinvar id is 1291574.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RARS2	NM_020320.5	c.*101del		3_prime_UTR_variant	20/20	ENST00000369536.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARS2	ENST00000369536.10	c.*101del		3_prime_UTR_variant	20/20	1	NM_020320.5	P1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 40103 AN: 112054 Hom.: 5427 Cov.: 0

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.360

GnomAD4 exome AF: 0.324 AC: 146095 AN: 450676 Hom.: 587 AF XY: 0.326 AC XY: 78850 AN XY: 242066

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.385

Gnomad4 ASJ exome AF: 0.337

Gnomad4 EAS exome AF: 0.310

Gnomad4 SAS exome AF: 0.351

Gnomad4 FIN exome AF: 0.327

Gnomad4 NFE exome AF: 0.317

Gnomad4 OTH exome AF: 0.322

GnomAD4 genome AF: 0.358 AC: 40096 AN: 112082 Hom.: 5428 Cov.: 0 AF XY: 0.360 AC XY: 19225 AN XY: 53374

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.357

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5878032; hg19: chr6-88224029;